Infections with oncogenic types of HPV cause virtually all cases of cervical cancer worldwide. Prophylactic and or combined prophylactic and early therapeutic types of vaccination against HPV 16 and 18, two of the most important HPV type, could protect against a large majority of the cases of cervical cancer globally. Vaccines based on the L1 structural protein of HPV which self-assemble into conformationally-correct virion-like particles (virus-like particles or VLPs) are under study. The immunogenicity and safety of HPV 16 & 18 VLPs have been demonstrated in Phase 1 and Phase 2 human trials. Evidence also suggest high efficacy of VLP-based vaccines in protecting against type-specific persistent HPV infection. A pivotal, full-scale Phase 3 randomized controlled trial of an HPV16/18 VLP vaccine will be fielded soon. Costa Rica was chosen for the Phase 3 trial because of our extensive successful scientific collaborations there, the continued high risk of cervical cancer, the universal medical system providing national linkage, and the likelihood of very high participation over the many needed years of close clinical follow-up. Over 10,000 women will be vaccinated according to current plans. In support of the vaccine trials, a variety of methodologic and ancillary projects are underway or planned, that will maximize the yield of the main effort.